Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function

Nature. 2005 Jun 23;435(7045):1113-6. doi: 10.1038/nature03648.


Vertebrate HoxA and HoxD cluster genes are required for proper limb development. However, early lethality, compensation and redundancy have made a full assessment of their function difficult. Here we describe mice that are lacking all Hoxa and Hoxd functions in their forelimbs. We show that such limbs are arrested early in their developmental patterning and display severe truncations of distal elements, partly owing to the absence of Sonic hedgehog expression. These results indicate that the evolutionary recruitment of Hox gene function into growing appendages might have been crucial in implementing hedgehog signalling, subsequently leading to the distal extension of tetrapod appendages. Accordingly, these mutant limbs may be reminiscent of an ancestral trunk extension, related to that proposed for arthropods.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning
  • Forelimb / embryology*
  • Gene Deletion*
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Mice
  • Multigene Family / genetics
  • Signal Transduction
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Hedgehog Proteins
  • Homeodomain Proteins
  • Trans-Activators